Mutations usually cause the production of altered proteins. By screening many individuals for the presence of altered proteins one can hope to gain information concerning the numbers of mutations in natural populations. Unfortunately the screening methods used to date usually can detect only those mutant proteins whose surface electrical charge is altered. We aim to develop a screening method that will detect altered proteins regardless of whether the mutation has affected their charge. An unbiased estimate of the frequency of mutations in natural populations may therefore result. The protein we will use for our investigations is the human red blood cell protein hemoglobin. Mutations affecting this protein are known to cause a number of human blood diseases, such as sickle cell anemia. In view of the possible mutagenic effects of environmental pollutants, pesticides, and food additives, such studies are particularly timely.